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Biomedical subjects

L Li

Publications and source records attributed to L Li.

At least 73 records · Page 4Linked to original sources
PubMed2005

Decreases in phosphoinositide-3-kinase/Akt and extracellular signal-regulated kinase 1/2 signaling activate components of spinal motoneuron death.

Motoneuron dependence on target-derived trophic factors during development is well established, with loss of trophic support leading to the death of these cells. A complete understanding of the intracellular signal transduction machinery associated with extracellular survival signals requires the examination of individual pathways in various cellular and environmental contexts. In cells deprived of trophic support, and hence compromised for survival, phosphoinositide-3-kinase (PI3K) is decreased when compared with healthy cells supplied with trophic support. Extracellular signal-regulated kinase 1/2 (ERK1/2) signaling is dramatically decreased in deprived cells. We have examined the role of these two pathways to understand how changes in their activity regulate motoneuron survival and death. Pharmacological inhibition of PI3K attenuated motoneuron survival and was important in the regulation of Bcl-2 serine phosphorylation, limited release of cytochrome c into the cytoplasm and caspase activation. Bax translocation from cytoplasm to mitochondria was not altered when PI3K was inhibited. High levels of ERK1/2 inhibition robustly attenuated motoneuron survival in cells supplied with trophic support, whereas moderate inhibition of ERK1/2 activation had little effect. ERK1/2 inhibition in these cells decreased Bcl-2 phosphorylation and resulted in release of cytochrome c from the mitochondria. Bax translocation and caspase activation were not affected by ERK1/2 inhibition. These data reveal that changes in PI3K and ERK1/2 signaling lead to individual and overlapping effects on the cell-death machinery. Characterizing the role of these pathways is critical for a fundamental understanding of the development and degeneration of specific neuronal populations.

Animals↗
PubMed2005

Design and fabrication of a microlens array by use of a slow tool servo.

In recent years it has become possible to fabricate free-form optics by use of multiaxis ultraprecision machines. Here a 5 x 5 microlens array is fabricated by using an ultraprecision diamond turning machine equipped with four independent axes. Unlike the conventional process where a single diamond tool is used to machine one lens at a time, this research demonstrates the development of an innovative diamond tool trajectory that allows the entire microlens array to be machined in a single operation. The machined microlens array is measured for both curve conformity and surface roughness. Compared to the conventional approach where indexing the workpiece is difficult and unreliable, this process can produce microlenses with accurate geometry and optical surface finish. This unique process is described in detail from optical measurement to machining process design and development to final results. This research also demonstrates the possibility of fabricating any arbitrary shape with the same approach.

Journal Article↗
PubMed2005

Selected growth of cubic and hexagonal GaN epitaxial films on polar MgO(111).

Selected molecular beam epitaxy of zinc blende (111) or wurtzite (0001) GaN films on polar MgO(111) is achieved depending on whether N or Ga is deposited first. The cubic stacking is enabled by nitrogen-induced polar surface stabilization, which yields a metallic MgO(111)-(1 x 1)-ON surface. High-resolution transmission electron microscopy and density functional theory studies indicate that the atomically abrupt semiconducting GaN(111)/MgO(111) interface has a Mg-O-N-Ga stacking, where the N atom is bonded to O at a top site. This specific atomic arrangement at the interface allows the cubic stacking to more effectively screen the substrate and film electric dipole moment than the hexagonal stacking, thus stabilizing the zinc blende phase even though the wurtzite phase is the ground state in the bulk.

Journal Article↗
PubMed2005

Disruption of an exon splicing enhancer in exon 3 of MLH1 is the cause of HNPCC in a Quebec family.

BACKGROUND: A 3 bp deletion located at the 5' end of exon 3 of MLH1, resulting in deletion of exon 3 from RNA, was recently identified. HYPOTHESIS: That this mutation disrupts an exon splicing enhancer (ESE) because it occurs in a purine-rich sequence previously identified as an ESE in other genes, and ESEs are often found in exons with splice signals that deviate from the consensus signals, as does the 3' splice signal in exon 3 of MLH1. DESIGN: The 3 bp deletion and several other mutations were created by polymerase chain reaction mutagenesis and tested using an in vitro splicing assay. Both mutant and wild type exon 3 sequences were cloned into an exon trapping vector and transiently expressed in Cos-1 cells. RESULTS: Analysis of the RNA indicates that the 3 bp deletion c.213_215delAGA (gi:28559089, NM_000249.2), a silent mutation c.216T-->C, a missense mutation c.214G-->C, and a nonsense mutation c.214G-->T all cause varying degrees of exon skipping, suggesting the presence of an ESE at the 5' end of exon 3. These mutations are situated in a GAAGAT sequence 3 bp downstream from the start of exon 3. CONCLUSIONS: The results of the splicing assay suggest that inclusion of exon 3 in the mRNA is ESE dependent. The exon 3 ESE is not recognised by all available motif scoring matrices, highlighting the importance of RNA analysis in the detection of ESE disrupting mutations.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Glucagon-like peptide-1 protects beta cells from cytokine-induced apoptosis and necrosis: role of protein kinase B.

AIMS/HYPOTHESIS: The gut hormone glucagon-like peptide-1 (GLP-1) decreases beta cell apoptosis in a protein kinase B (PKB)-dependent fashion, and increases islet cell mass and function in vivo. In contrast, cytokines induce beta cell apoptosis, leading to decreased islet mass and type 1 diabetes. In the present study we used rat INS-1E beta cells and primary rat islet cells to examine the potential role of PKB as a mediator of the effect of GLP-1 on cytokine-induced apoptosis. METHODS: Cell viability was determined by MTT assay, and apoptosis and necrosis by Hoechst 33342-propidium iodide staining. Immunoblot analysis was used to detect changes in protein expression, including active (phosphorylated) and total PKB, phosphorylated and total glycogen synthase kinase-3beta, activated caspase-3 and inducible nitric oxide synthase. Reactive oxygen species were determined by 1,7-dichlorofluorescein (DCF) analysis, and mutant forms of PKB were introduced into cells using adenoviral vectors. RESULTS: Incubation of INS-1E cells with cytokines (IL-1beta, TNF-alpha and interferon-gamma; 10-50 ng/ml) for 18 h significantly decreased cell viability (by 44%, p<0.001), cell proliferation (by 80%, p<0.001), and activation of PKB (by 67%, p<0.001). Pre-treatment with exendin-4 (10(-7) mol/l), a long-acting GLP-1 receptor agonist, partially protected the cells against cytokine-induced toxicity (p<0.01) in association with a reduction in cytokine-induced inhibition of PKB phosphorylation (p<0.05). Exendin-4 pre-treatment did not change cell proliferation. Cytokine treatment increased apoptosis (by 156%, p<0.05) and necrosis (from undetectable to 2.6% of cells). These increases were both reduced by pre-treatment with exendin-4 (p<0.05-0.01). Furthermore, cytokine-induced apoptosis and necrosis were significantly increased in cells infected with kinase-dead PKB (p<0.05), and the protective effect of exendin-4 on both parameters was fully abolished in these cells. Similar changes were observed in primary islet cells. In parallel with these changes, exendin-4 decreased the cytokine-induced activation of caspase-3 (by 46%, p<0.05), and decreased levels of inducible nitric oxide synthase (by 71%, p<0.05) and reactive oxygen species (by 27%, p<0.05). CONCLUSIONS/INTERPRETATION: The results of our study indicate that GLP-1 plays a protective role against cytokine-induced apoptosis and necrosis in beta cells through a PKB-dependent signalling pathway.

Animals↗
PubMed2005

Short-length microstructured phosphate glass fiber lasers with large mode areas.

We report fabrication and testing of the first phosphate glass microstructured fiber lasers with large Er-Yb-codoped cores. For an 11-cm-long cladding-pumped fiber laser, more than 3 W of continuous wave output power is demonstrated, and near single-mode beam quality is obtained for an active core area larger than 400 microm2.

Journal Article↗
PubMed2005

Anti-sulfatide antibodies in HIV-infected individuals with sensory neuropathy.

We used ELISA to estimate the prevalence of anti-sulfatide antibodies in HIV-infected individuals with distal sensory neuropathy (DSP) and compared the results with the prevalence in HIV-infected individuals without DSP and in individuals with neuropathy who are not infected with HIV. We found that 36% of HIV+/DSP+ individuals had immunoglobulin (Ig) G anti-sulfatide antibody titers greater than 1,500, whereas IgG anti-sulfatide antibodies were rarely found in HIV+/DSP- or HIV-/DSP+ patients.

Autoantibodies↗
PubMed2005

Acupuncture for acute stroke.

BACKGROUND: Acupuncture-like sensory stimulation activates multiple efferent (nerve) pathways leading to altered activity in numerous neural systems. Acupuncture is widely accepted by Chinese people and it is increasingly requested by patients and their relatives in Western countries. OBJECTIVES: To assess the effectiveness and safety of acupuncture in patients with acute stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (last searched August 2003), the Chinese Stroke Trials Register (August 2003) and the Chinese Acupuncture Trials Register (August 2003). Electronic searches were performed in the Cochrane Controlled Trials Register (The Cochrane Library, Issue 3, 2003), MEDLINE (1966 to 2003), EMBASE (1980 to 2003), Alternative Medicine Database (1985 to 2003), CINAHL (1982 to 2003) and the Chinese Biological Medicine Database (1981 to 2003). Reference lists of systematic reviews and identified trials were handsearched. SELECTION CRITERIA: Randomised and quasi-randomised trials of acupuncture started within 30 days of stroke onset, compared with placebo/sham acupuncture or open control in patients with acute ischaemic and/or haemorrhagic stroke. Needling into skin was required for acupuncture. DATA COLLECTION AND ANALYSIS: Two reviewers selected trials for inclusion, assessed trial quality, and extracted the data independently. Authors of trials were contacted for missing data. MAIN RESULTS: Fourteen trials involving 1208 patients were included. Ten trials included patients with only ischaemic stroke. When acupuncture was compared with sham acupuncture or open control, there was a borderline significant trend towards fewer patients being dead or dependent (Odds ratio (OR) 0.66, 95% confidence interval (CI) 0.43 to 0.99), and significantly fewer being dead or needing institutional care (OR 0.58, 95% CI 0.35 to 0.96) in the acupuncture group after three months or more. There was also a significant difference favouring acupuncture in the mean change of global neurological deficit score during the treatment period (standardized mean difference (SMD) 1.17, 95% CI 0.30 to 2.04). Comparison of acupuncture with sham acupuncture only showed a statistically significant difference on death or requiring institutional care (OR 0.49, 95% CI 0.25 to 0.96), but not on death or dependency (OR 0.67, 95% CI 0.40 to 1.12), or change of global neurological deficit score (SMD 0.01, 95% CI -0.55 to 0.57). Severe adverse events with acupuncture (dizziness, intolerable pain and infection of acupoints) were rare (6/386, 1.55%). AUTHORS' CONCLUSIONS: Acupuncture appeared to be safe but without clear evidence of benefit. The number of patients is too small to be certain whether acupuncture is effective for treatment of acute ischaemic or haemorrhagic stroke. Larger, methodologically-sound trials are required.

Acupuncture Therapy↗
PubMed2005

Enhancement of cyanide-induced mitochondrial dysfunction and cortical cell necrosis by uncoupling protein-2.

Uncoupling protein 2 (UCP-2) is expressed in the inner mitochondrial membrane and modulates mitochondrial function by partially uncoupling oxidative phosphorylation, and it has been reported to modulate cell death. Cyanide is a potent neurotoxin that inhibits complex IV to alter mitochondrial function to induce neuronal death. In primary rat cortical cells KCN produced an apoptotic death at 200-400 microM. Higher concentrations of potassium cyanide (KCN) (500-600 microM) switched the mode of death from apoptosis to necrosis. In necrotic cells, ATP levels were severely depleted as compared to cortical cells undergoing apoptosis. To determine if UCP-2 expression could alter KCN-induced cell death, cells were transiently transfected with full-length human UCP-2 cDNA (UCP-2+). Overexpression switched the mode of death produced by KCN (400 microM) from apoptosis to necrosis. The change in cell death was mediated by impaired mitochondrial function as reflected by a marked decrease of ATP levels and reduction in mitochondrial membrane potential. RNA interference or transfection with a dominant interfering mutant blocked the necrotic response observed in UCP-2+ cells. Additionally, treatment of UCP-2+ cells with cyclosporin A blocked necrosis, indicating the involvement of mitochondrial permeability pore transition in the necrotic death. These results show that increased expression of UCP-2 alters the response to a potent mitochondrial toxin by switching the mode of cell death from apoptosis to necrosis. It is concluded that UCP-2 levels influence cellular responses to cyanide-induced mitochondrial dysfunction.

Animals↗
PubMed2005

Antioxidant activity of gallic acid from rose flowers in senescence accelerated mice.

The activities of the antioxidant enzymes catalase (CAT) and glutathione peroxidase (GPx) in the blood and liver of the aging model induced by injection of different doses of D-gal into normal mice, and in senescence accelerated mice (SAM) of different ages, were determined. The results showed that the enzyme activities in the D-gal treated mice did not alter appreciably but the enzyme activities in blood of the SAM declined significantly with the increase in age, especially in the 9-month-old SAM. When gallic acid purified from rose flowers was used to treat the 9-month-old male SAM, it not only reinstated the activities of CAT and GPx but also significantly reduced the amount of malondialdehyde (MDA) in the liver, brain and kidney. The results demonstrated that 9-month-old male SAM represent an appropriate animal model to evaluate the antioxidant activities of natural products.

Aging↗
PubMed2005

Use of CD34+ autologous stem cell transplantation in the treatment of children with refractory systemic lupus erythematosus.

We report on the unique effects and benefits of autologous stem cell transplantation in childhood systemic lupus erythematosus (SLE) and describe this procedure in two young girls with severe and refractory disease. The patients' stem cells were mobilized with granulocyte colony-stimulating factor (G-CSF) and collected by CS-3000 Blood Cell Separator (Baxter Healthcare, Round Lake, Ill., USA), and the CliniMACS CD34+ cell selection device (Miltenyi Biotech, Bergisch Gladbach, Germany) was used to obtain CD34+ cells. A total of 1.7x10(6) and 1.0x10(6)/kg CD34+ cells were obtained, with 2.0x10(5) and 1.0x10(4)/kg of CD3+ cells remaining, respectively. The conditioning regimen consisted of cyclophosphamide (50 mg/kg per day for 4 days) plus antithymocyte globulin (ATG-Fresenius, 5 mg/kg per day for 3 days). Neutrophil counts recovered within 9 days in both cases. Within 15 days, the platelet counts recovered and were sustained over 100x10(9)/l. Cushingoid features disappeared completely 3 months after transplantation because of the removal of corticosteroid medication. One 13-year-old child increased her height by 5 cm in 6 months after stopping steroids. She had not increased her height in her previous 7 years of disease. As of the time of this report, the first patient remains in clinical and laboratory remission for nearly 4 years, while the second suffered a relapse of thrombocytopenia 9 months post-transplantation. One residual effect of their treatment is that their CD4+ cell counts remained in the lower range after one year of transplant. The effect of this conditioning regimen plus CD34+ autologous stem cell transplantation on these two children with refractory SLE was beneficial, but long-term follow-up data and additional experience with this procedure are required. Autologous stem cell transplantation may limit the long-term toxicity of therapy in childhood SLE.

Adolescent↗
PubMed2005

Variation of CD4+ and CD8+ T lymphocytes as predictor of outcome in renal allograft recipients who developed acute respiratory distress syndrome caused by cytomegalovirus pneumonia.

INTRODUCTION: We investigated the variation of CD4+ and CD8+ T lymphocytes in renal allograft recipients who developed acute respiratory distress syndrome (ARDS) caused by cytomegalovirus (CMV) infection and their relationship to patients outcome. METHODS: Twenty one cadaveric renal allograft recipients who developed ARDS caused by CMV infection were enrolled in this study. CD4+ and CD8+ T lymphocytes were examined in peripheral blood on five occasions: the admission day (day 0) to ICU as ARDS, day 5, day 10, day 15 in ICU, and discharge day. A value taken in the second month after transplantation was assumed to be the preinfection value. RESULTS: Among 13 surviving patients, the numbers of CD4+ and CD8+ T cells and their ratio increased as the patients recovered. The numbers of CD4+ T cells increased significantly on day 10, day 15, and at discharge day compared with day 0 (P < .05). The number of CD8+ T cells on discharge day and the ratios after day 10 were also significantly higher than those on day 0 (P < .05). In eight nonsurviving patients, the numbers of CD4+ and CD8+ T cells and their ratio was similar to day 0. The number of CD4+ and CD8+ cells after day 5 and their ratio after day 10 were significantly lower than those of survival group (P < .05). CONCLUSION: The variations of CD4+ and CD8+ T lymphocytes and their ratio are useful indicators of the severity of disease and the outcome of patients with CMV infections accompanying ARDS after renal transplantation. Nevertheless, it may be helpful to evaluate the efficiency of ongoing treatment methods in these patients.

CD4 Lymphocyte Count↗
PubMed2005

Late developing C4d-positive humoral renal allograft rejection associated with withdrawal of mycophenolate mofetil.

In renal transplantation, C4d-positive acute humoral rejection (AHR) usually develops in the early stage posttransplantation. It is clear C4d can be detected late after the operation, when it is associated with chronic renal allograft rejection. We report a case of a renal allograft recipient who experienced C4d-positive acute renal allograft rejection associated with withdrawal of mycophenolate mofetil (MMF) at 10 months after transplantation. This 21-year-old single male patient received his first cadaveric renal allograft under immunosuppression with cyclosporine, MMF, and prednisolone. The serum creatinine recovered to the normal range within 4 days. A protocol biopsy performed at 1 month after transplantation revealed no signs of rejection. The graft function was stable until 10 months postoperation, when MMF was converted to mizoribin. Three days later a biopsy showed a C4d-positive rejection. Patient had no response to the MMF combined with tacrolimus and steroid bolus therapy, which generally improves 85% of AHR among Chinese. He finally returned to dialysis. Our report suggested that C4d positive AHR may occur late after transplantation. MMF is important to suppress the body's humoral response to allograft; when MMF was converted to a weaker immunosuppressant, the dose of the other immunosuppressants (cyclosporine for example) must be adjusted properly.

Acute Disease↗
PubMed2005

The emerging role of the PI3-K-Akt pathway in prostate cancer progression.

The PI3-K-Akt pathway plays a central role in the development and progression of prostate cancer and other malignancies. We review original studies and summarize relevant sections of previous reviews concerning the relationships between abnormalities in the PI3-K-Akt pathway and prostate cancer progression. We discuss laboratory and clinical data that indicate gene perturbation and dysregulation of PI3-K-Akt pathway is common in prostate cancer and other malignancies. We further discuss the critical role of the PI3-K-Akt pathway in the oncogenic signaling network and provide examples that establish the PI3-K-Akt pathway as a focal point for the future development of informative biomarkers and effective therapies for prostate cancer.

Biomarkers, Tumor↗
PubMed2005

Statistics on cancer in China: cancer registration in 2002.

The objective of this study was to determine how many population-based cancer registries exist in China, what methods are being used, and the statistical data that are available from them, and to identify future needs with respect to technical support. A two-stage survey was conducted in 2002 at provincial and cancer registry level. Based on the questionnaire used in these two stages, the basic distribution and descriptive information on population-based cancer registry practices in China are addressed. There are 48 cancer registries in China, covering 73 million people (5.7% of the total population of China in 2000). The oldest three registries are LinZhou, ShangHai and QiDong. There are marked variations in practice between registries, with respect to data collection, data management and coding. Differences are also found in administrative aspects and sources of financial support. In conclusion, this first national survey of Chinese cancer registry practice provides a benchmark against which development and standardization can be evaluated in the future. The survey suggests that lack of qualified personnel, insufficient funding support and lack of stability of the population are major problems in carrying out registration work in China. It also indicates several ways in which registry practice, and hence availability and quality of incidence and survival data can be improved.

Benchmarking↗
PubMed2005

Construction of transgenic Bacillus mucilaginosus strain with improved phytase secretion.

AIMS: To construct a transgenic Bacillus mucilaginosus strain to increase the secretion capability of a wild-type isolate of B. mucilaginosus D4B1 to hydrolyse phytate phosphorus, which can be used as a microbial fertilizer in field application. METHODS AND RESULTS: We constructed a phytase secreting expression vector pSP43 with a mini-Tn5 transposon and a Aspergillus fumigatus phytase expression cassette. The vector pSP43 was successfully transferred into the wild-type B. mucilaginosus using the particle bombardment method, and three transgenic strains with a stable copy of phytase expression cassette integrated into the chromosome of the B. mucilaginosus by Tn5 transposition were selected. The phytase activity of the engineered strains increased 36-46-fold when compared with the wild-type strain of D4B1. CONCLUSIONS: The A. fumigatus phytase gene can be expressed under the direction of p43 promoter in B. mucilaginosus. The expression protein is secreted extracellularly and newly constructed strains showed a high phytase activity. SIGNIFICANCE AND IMPACT OF THE STUDY: A transgenic Bacillus strain by the particle bombardment method was constructed.

6-Phytase↗